Quantitative EM autoradiography has been used as a visual probe. In an attempt to use a higher resolution probe in hormone binding studies cationic ferritin has been employed. Cationic ferritin initially binds to the villous surface of the cell, is subsequently localized in coated pits and then internalized. The material is internalized first into coated vesicles and then into a series of membrane bounded vesicles of increasing size. This is analogous to the pattern that has been observed with iodide labeled insulin in 3T3-L1 adipocytes. The process of receptor-mediated endocytosis appears to be relatively non-specific with respect to the various structures involved. Previously an autoantibody to the insulin receptor, when labeled with iodine and cytoabsorbed for purification, binds to cell surfaces and is internalized in an analogous fashion to insulin. Recent studies show that the univalent Fab fragment is processed in an identical fashion to both insulin and to the divalent receptor antibody. The U-937 monocyte-like cultured cell, a model for circulating monocytes, binds and internalizes insulin in an analogous fashion to target cells such as liver cells. The U-937 monocyte internalizes insulin at a high rata and the addition of monensin to insulin markedly augments down regulation of receptor. By contrast, the IM-9 lymphocyte which internalizes insulin poorly, shows essentially no additional effect when monensin is added. The drug colchicine which inhibits endosomal transfer to lysosomes in hepatocytes has been studied. There is no localization to an additional compartment such as the Golgi with respect to processing of an internalized ligand. The internal route appears to go from the endosome of one or more types to the lysosome of one or more types; the recycling process would appear to occur from either of the two membrane-bounded structures.